Abstract

Rheumatoid arthritis (RA) is a common, systemic autoimmune disease of which the exact etiology is not known. In the past 10 years, substantial progress has been made in the identification of the antigens specifically recognized by the autoantibodies of RA patients. A central factor in this respect is citrullination, a form of post-translational modification that is strongly associated with autoimmunity in RA. Here, we summarize and discuss our current knowledge on (i) autoantibody systems in RA, (ii) the occurrence of peptidylarginine deiminases and (iii) citrullinated proteins in natural and diseased environments, and (iv) genetic factors involved in RA that may influence the generation and presentation of citrullinated proteins and the resulting antibody production against these modified proteins. Citrullination of proteins may play a key role in the initiation and/or the progression of RA. The onset of citrulline-specific autoimmunity in RA is probably mediated by both environmental and genetic factors, and future studies will learn whether therapeutic intervention at the level of citrullination may provide new possibilities to treat RA.